Abstract <p><i>Miliusa nilagirica Bedd</i>. (Annonaceae), an endemic species of the Western Ghats, exhibits a rich secondary metabolite profile and notable ethnomedicinal potential. This study evaluated its antioxidant, antidiabetic, cytotoxic, and toxicity profiles to validate its pharmacological relevance. <i>M. nilagirica</i> carbinolic extract (MNCE) demonstrated the highest antioxidant and antidiabetic activities among tested extracts in DPPH (53.72%), phosphomolybdenum (455.11&#xa0;mg AAEAC/g extract), nitric oxide radical scavenging (81.48%) and lipid peroxidation assays (70.89%). GC–MS analysis revealed diverse bioactive phytoconstituents and no substantial toxicity arose from ADMET analysis. In vitro cytotoxic evaluation showed MNCE to be non-toxic toward normal cell lines (RIN-5F and SH-SY5Y) but selectively toxic to cancerous PANC-1 (IC₅₀ = 3.86&#xa0;mg/L) and MDA-MB- 231 (IC₅₀ = 4.95&#xa0;mg/L) cells, suggesting its dual potential in β-cell protection and targeted cancer therapy. In vivo acute toxicity tests revealed no mortality or behavioral abnormalities up to 2000&#xa0;mg/kg. Subacute (28-day) administration at 50–200&#xa0;mg/kg produced no significant changes in body weight, hematological or biochemical parameters, and histopathological examination confirmed the absence of organ-specific toxicity. Collectively, the high antioxidant and antidiabetic efficacy, selective cytotoxicity, and strong safety profile highlight <i>M. nilagirica</i> carbinolic extract as a promising candidate for chronic disease management, particularly diabetes-associated oxidative stress and cancer intervention.</p> Highlights <p><i>Miliusa nilagirica</i> leaf extracts show strong antioxidant and antidiabetic activity.</p> <p>MNCE is non-toxic to RIN-5F, SH-SY5Y, but targets PANC-1, MDA-MB-231 cancer cells.</p> <p>No mortality or organ toxicity in acute (2000 mg/kg) and subacute (50–200 mg/kg) tests.</p> <p>Organ structure and weights remain stable, supporting MNCE’s safety for long-term use.</p> <p>MNCE preserves β-cells in diabetes and selectively targets cancer cells.</p> Graphical Abstract <p></p>

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Phytochemical Profiling and Subacute Toxicity Assessment of Miliusa nilagirica Carbinolic Extract in Murine Models With Antioxidant and Antidiabetic Potential

  • Francis Jegan Raj,
  • Vetri Velavan Sundararajan,
  • Anish Ruban S,
  • Parimelazhagan Thangaraj

摘要

Abstract

Miliusa nilagirica Bedd. (Annonaceae), an endemic species of the Western Ghats, exhibits a rich secondary metabolite profile and notable ethnomedicinal potential. This study evaluated its antioxidant, antidiabetic, cytotoxic, and toxicity profiles to validate its pharmacological relevance. M. nilagirica carbinolic extract (MNCE) demonstrated the highest antioxidant and antidiabetic activities among tested extracts in DPPH (53.72%), phosphomolybdenum (455.11 mg AAEAC/g extract), nitric oxide radical scavenging (81.48%) and lipid peroxidation assays (70.89%). GC–MS analysis revealed diverse bioactive phytoconstituents and no substantial toxicity arose from ADMET analysis. In vitro cytotoxic evaluation showed MNCE to be non-toxic toward normal cell lines (RIN-5F and SH-SY5Y) but selectively toxic to cancerous PANC-1 (IC₅₀ = 3.86 mg/L) and MDA-MB- 231 (IC₅₀ = 4.95 mg/L) cells, suggesting its dual potential in β-cell protection and targeted cancer therapy. In vivo acute toxicity tests revealed no mortality or behavioral abnormalities up to 2000 mg/kg. Subacute (28-day) administration at 50–200 mg/kg produced no significant changes in body weight, hematological or biochemical parameters, and histopathological examination confirmed the absence of organ-specific toxicity. Collectively, the high antioxidant and antidiabetic efficacy, selective cytotoxicity, and strong safety profile highlight M. nilagirica carbinolic extract as a promising candidate for chronic disease management, particularly diabetes-associated oxidative stress and cancer intervention.

Highlights

Miliusa nilagirica leaf extracts show strong antioxidant and antidiabetic activity.

MNCE is non-toxic to RIN-5F, SH-SY5Y, but targets PANC-1, MDA-MB-231 cancer cells.

No mortality or organ toxicity in acute (2000 mg/kg) and subacute (50–200 mg/kg) tests.

Organ structure and weights remain stable, supporting MNCE’s safety for long-term use.

MNCE preserves β-cells in diabetes and selectively targets cancer cells.

Graphical Abstract